DOI: 10.1177/1934578x261476818 ISSN: 1934-578X

Anti-Neuroinflammatory Mechanisms of Strychnos nux-vomica L. in Bortezomib-Induced Peripheral Neuropathy: A Translational Study Integrating Network Pharmacology and Experimental Validation

Jingjing Xiang, Sichun Xiang, Ni Zhu, Mengke Mao, Lili Qian, Yu Zhang, Jianping Shen, Jun Yan, Shu Deng
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Objective

Bortezomib-induced peripheral neuropathy (BIPN) is a debilitating dose-limiting toxicity in multiple myeloma (MM) therapy. This study explored the potential clinical effects and anti-neuroinflammatory mechanisms of Strychnos nux-v omica L. ( N. vomica ) in BIPN by integrating exploratory clinical observation, network pharmacology, and in vitro experimental validation.

Methods

In a single-arm, open-label, self-controlled exploratory clinical study, 22 patients with MM-related BIPN received oral N. vomica capsules (NVC) for 6 weeks. Neuropathy-related clinical scores and serum inflammatory cytokines were evaluated at baseline and during treatment. Network pharmacology was performed to identify candidate compounds, putative targets, and enriched pathways. In vitro experiments using bortezomib-injured DRG-derived 50B11 cells examined cell viability and cytokine-related transcriptional responses after strychnine preconditioning.

Results

NVC treatment was associated with reductions in neuropathy-related clinical scores and selected serum inflammatory cytokines over the 6-week observation period. Network pharmacology identified 13 candidate bioactive compounds and 58 putative targets, with enrichment in inflammation-related pathways, including PI3K-AKT, MAPK, TNF, and NF-κB signaling. In vitro, strychnine preconditioning attenuated bortezomib-induced reduction in cell viability at 24 h, but this protective effect was not sustained at 48 or 72 h. Strychnine preconditioning also reduced bortezomib-induced transcriptional upregulation of IL-6, IL-17, IL-1β, and TNF-α.

Conclusion

This exploratory study provides preliminary evidence that NVC treatment may be associated with improvement in BIPN-related symptoms and reduced inflammatory cytokine levels. Network pharmacology and in vitro findings support a potential anti-neuroinflammatory role of N. vomica , although these findings require confirmation in adequately powered controlled clinical and mechanistic studies.

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